NMDI14 |
Catalog No.GC32744
One-Click Copy Product Info
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NMDI14 is potent inhibitor of nonsense mediated RNA decay (NMD).
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 307519-88-6
Sample solution is provided at 25 µL, 10mM.
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NMDI14 is potent inhibitor of nonsense mediated RNA decay (NMD)[1]. NMDI14 prevents the formation of the UPF1-SMG7 (or UPF1-SMG5) heterodimers, suppresses NMD and stabilizes W1282X mRNA [2]. NMDI14 has been widely used as a model compound to develop a series of derivatives and serve as anti-mesothelioma agents in vitro[3].
In vitro, NMDI14 treatment at 50μM for 6 hours significantly increased the expression level of p53 mRNA in U2OS cells, without affecting cell viability[4]. After treating primary nasal epithelial cells of W1282X heterozygous carriers with 5μM NMDI14 for 12 hours, the level of W1282X transcripts was significantly increased[5]. Treatment with 50 μM NMDI14 for 72 hours can prevent the upregulation of ABCC1 and ABCC2 mRNA mediated by human papilloma virus (HPV) 18 E6/E7 proteins in HNO206 cells[6]. 0.1μM of NMDI14 and CC-90009 (7.5nM) treatment for 2 days significantly promoted the increase in the expression of type XVII collagen in JEB-C17 keratinocytes without affecting cell viability[7].
In, vivo, NMDI14 treatment via intracerebroventricular injection (2μL; 674 μM) three times within 24h in a mouse model of status epilepticus significantly reduced the spontaneous epileptic seizures that occurred following the persistent state of epilepsy[8].
References:
[1] Evtushenko N, Beilin A, Novikov A, et al. 163 Nonsense-mediated mRNA decay inhibitors perspectives for recessive dystrophic epidermolysis bullosa treatment[J]. Journal of Investigative Dermatology, 2021, 141(10): S176.
[2] Ensinck M M, Carlon M S. One size does not fit all: the past, present and future of cystic fibrosis causal therapies[J]. Cells, 2022, 11(12): 1868.
[3] Nguyen H N, Suzuki K, Kimura Y, et al. Synthesis and biological evaluation of NMDI14 derivatives as anti-mesothelioma agents[J]. Heterocycles, 2020, 100(2): 253-266.
[4] Martin L, Grigoryan A, Wang D, et al. Identification and characterization of small molecules that inhibit nonsense-mediated RNA decay and suppress nonsense p53 mutations[J]. Cancer research, 2014, 74(11): 3104-3113.
[5] Aksit M A, Bowling A D, Evans T A, et al. Decreased mRNA and protein stability of W1282X limits response to modulator therapy[J]. Journal of Cystic Fibrosis, 2019, 18(5): 606-613.
[6] Rigalli J P, Reichel M, Tocchetti G N, et al. Human papilloma virus (HPV) 18 proteins E6 and E7 up-regulate ABC transporters in oropharyngeal carcinoma. Involvement of the nonsense-mediated decay (NMD) pathway[J]. Cancer letters, 2018, 428: 69-76.
[7] Sayar S B, Has C. Strategy for the optimization of read-through therapy for junctional epidermolysis bullosa with COL17A1 nonsense mutation[J]. Journal of Investigative Dermatology, 2024, 144(10): 2221-2229. e1.
[8] Mooney C M, Jimenez-Mateos E M, Engel T, et al. RNA sequencing of synaptic and cytoplasmic Upf1-bound transcripts supports contribution of nonsense-mediated decay to epileptogenesis[J]. Scientific reports, 2017, 7(1): 41517.
| Cell experiment [1]: | |
Cell lines | U2OS cells |
Preparation Method | U2OS cells were cultured in DMEM medium containing 10% fetal bovine serum. The cells were seeded in 6-well plates and after 24 hours, they were treated with NMDI14 (50μM) for 6 hours, and the expression of endogenous unmutated NMD targets was evaluated by real-time PCR. |
Reaction Conditions | 50μM; 6h |
Applications | NMDI14 treatment significantly enhanced the expression of p53 mRNA in U2OS cells. |
| Animal experiment [2]: | |
Animal models | Male C57BL/6 mice |
Preparation Method | Anesthetize male C57BL/6 mice with isoflurane and place them in a stereotactic frame, which is equipped with cranial-mounted recording electrodes. Perform a craniotomy and place a guiding catheter above the right amygdala of the skull. Secure the components in place, then place the mouse in a warm recovery room. Next, using the catheter, microinject KA (0.3 μg; 0.2μl) into the right amygdala of the freely moving mouse. Seizures begin within 5-10 minutes and progressively worsen, becoming persistent epilepsy after approximately 30 minutes. 40 minutes after the KA seizure, administer lorazepam (8mg/kg; intraperitoneal injection) to reduce morbidity and mortality and limit the degree of hippocampal damage. Additional craniotomies were performed during the intracranial injection of the electrodes and guiding catheters. At 1, 4, and 24 hours after the lorazepam termination of the seizures, inject NMDI14 (2μl; 674 μM) into the ventricles, achieving a final ventricular NMDI14 concentration of approximately 50μM, for continuous video electroencephalogram monitoring of the mice. |
Dosage form | 2μl 674 μM three times a day for 1 day; i.c.v |
Applications | NMDI14 treatment reduced spontaneous epileptic seizures after status epilepticus in mice. |
References: | |
| Cas No. | 307519-88-6 | SDF | |
| Canonical SMILES | O=C(C1=C(NC(CC2NC3=C(C=C(C)C(C)=C3)NC2=O)=O)SC(C)=C1C)OCC | ||
| Formula | C21H25N3O4S | M.Wt | 415.51 |
| Solubility | DMSO : ≥ 25 mg/mL (60.17 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4067 mL | 12.0334 mL | 24.0668 mL |
| 5 mM | 481.3 μL | 2.4067 mL | 4.8134 mL |
| 10 mM | 240.7 μL | 1.2033 mL | 2.4067 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 29 reference(s) in Google Scholar.)